Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture.
Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture.
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DOI：
10.1016/j.cell.2018.07.042
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发表时间：
2018-09-20
期刊：
影响因子：
64.5
通讯作者：
Amon A
中科院分区：
文献类型：
--
作者：
Knouse KA;Lopez KE;Bachofner M;Amon A
我们对染色体分离的大部分理解是基于细胞培养系统。在这里，我们通过比较几种原代细胞类型在原生和非原生环境下的染色体分离保真度来研究组织环境对染色体分离的重要性。我们发现上皮细胞在其原生组织外增加了染色体错分离。使用类器官培养系统，我们表明组织结构，特别是整合素功能，是准确的染色体分离所必需的。我们发现组织结构增强了端粒微管-着丝点附着物的校正，这对于维持多倍体肝脏中染色体的稳定性尤其重要。我们提出组织结构的破坏可能是上皮性癌症中广泛存在的染色体不稳定性的基础。此外，我们的研究结果强调了细胞外环境可以影响内在细胞过程的程度，以及研究组织内自然功能细胞的细胞培养系统的局限性。组织结构和整合素功能是支持上皮组织中染色体分离保真度的关键因素
Much of our understanding of chromosome segregation is based on cell culture systems. Here, we examine the importance of the tissue environment for chromosome segregation by comparing chromosome segregation fidelity across several primary cell types in native and nonnative contexts. We discover that epithelial cells have increased chromosome missegregation outside of their native tissues. Using organoid culture systems, we show that tissue architecture, specifically integrin function, is required for accurate chromosome segregation. We find that tissue architecture enhances the correction of merotelic microtubule-kinetochore attachments and this is especially important for maintaining chromosome stability in the polyploid liver. We propose that disruption of tissue architecture could underlie the widespread chromosome instability across epithelial cancers. Moreover, our findings highlight the extent to which extracellular context can influence intrinsic cellular processes and the limitations of cell culture systems for studying cells that naturally function within a tissue. Tissue architecture and integrin function are critical factors that support chromosome segregation fidelity in epithelial tissues
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